African Americans (AA) are at risk for clinical pain, though the biopsychosocial mechanisms underlying enhanced pain in AAs are unknown. Relative to Caucasians, our prior work found that AAs show blunted responses of the hypothalamic-pituitary-adrenal (HPA) and sympathetic nervous system axes (SNS), and also lower oxytocin (OT) and allopregnanolone (AP), and the absence of relationship to pain sensitivity during activation of these stress-responsive systems. The relationship of these stress-responsive factors to pain sensitivity is thought to reflect an integrated response during the defense reaction. Blunted stress responses and an uncoupling of the relationship between stress responses and pain sensitivity in AAs are hypothesized to result from excessive activation of these stress systems resulting from chronic psychosocial stress in AAs. A total of 280 medically healthy AA men and women (18 - 45 years of age) will be recruited to reflect the entire SES spectrum. Interviews will access psychosocial stress, including cumulative trauma exposure, chronic stress (i.e., discrimination and difficulties), and recent negative life events. Also, potential stress buffers (e.g. religiosity, social support) will be assessed. Subjects will undergo one laboratory test session to assess pain sensitivity and endogenous pain regulatory mechanisms. Subjects will be tested while supine for baroreceptor reflex sensitivity, involving EKG measurement of heart rate and beat-to-beat changes in BP. Each subject will be tested for an index of central sensitization of pain processing by administration of a repetitive application of transient heat pulses for a maximum of 40 trials or until the subject rates the intensity of the stimulus at 100 (0-100 scale). The assessment of centrally-mediated pain inhibition will be conducted by repeating the application of transient heat pulses during concurrent hand cold presser stimulation to assess for diffuse noxious inhibitory controls (DNIC). Voluntary pain tolerance to tourniquet-induced ischemia will also be assessed. Each subject will also be exposed to the Trier Social Stress Test in order to assess stress-induced HPA and SNS reactivity. The relationship of psychosocial stress to endogenous pain regulatory mechanisms, central pain processing and peripheral pain sensitivity, and the role of stress buffers will be examined using structural equation modeling. This proposal is intended to forge new territory in the development of a bio-behavioral model relating to the development of clinical pain in African Americans. Project Description